Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics
- Fassier, C., Fréal, A., Gasmi, L., Delphin, C., Ten Martin, D., De Gois, S., Tambalo, M., Bosc, C., Mailly, P., Revenu, C., Peris, L., Bolte, S., Schneider-Maunoury, S., Houart, C., Nothias, F., Larcher, J.C., Andrieux, A., Hazan, J.
- The Journal of cell biology 217(5): 1719-1738 (Journal)
- Registered Authors
- Hazan, Jamile, Houart, Corinne, Revenu, Celine, Schneider-Maunoury, Sylvie
- MeSH Terms
- Adenosine Triphosphatases/chemistry
- Adenosine Triphosphatases/metabolism*
- Axon Guidance*
- Gene Knockdown Techniques
- Growth Cones/metabolism
- Microtubule-Associated Proteins/metabolism
- Motor Neurons/metabolism
- Nuclear Proteins/chemistry
- Nuclear Proteins/metabolism*
- Protein Isoforms/metabolism
- Spinal Cord/metabolism
- 29535193 Full text @ J. Cell Biol.
Fassier, C., Fréal, A., Gasmi, L., Delphin, C., Ten Martin, D., De Gois, S., Tambalo, M., Bosc, C., Mailly, P., Revenu, C., Peris, L., Bolte, S., Schneider-Maunoury, S., Houart, C., Nothias, F., Larcher, J.C., Andrieux, A., Hazan, J. (2018) Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics. The Journal of cell biology. 217(5):1719-1738.
During neural circuit assembly, extrinsic signals are integrated into changes in growth cone (GC) cytoskeleton underlying axon guidance decisions. Microtubules (MTs) were shown to play an instructive role in GC steering. However, the numerous actors required for MT remodeling during axon navigation and their precise mode of action are far from being deciphered. Using loss- and gain-of-function analyses during zebrafish development, we identify in this study the meiotic clade adenosine triphosphatase Fidgetin-like 1 (Fignl1) as a key GC-enriched MT-interacting protein in motor circuit wiring and larval locomotion. We show that Fignl1 controls GC morphology and behavior at intermediate targets by regulating MT plus end dynamics and growth directionality. We further reveal that alternative translation of Fignl1 transcript is a sophisticated mechanism modulating MT dynamics: a full-length isoform regulates MT plus end-tracking protein binding at plus ends, whereas shorter isoforms promote their depolymerization beneath the cell cortex. Our study thus pinpoints Fignl1 as a multifaceted key player in MT remodeling underlying motor circuit connectivity.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes